Synergistic induction of miR-126 by hypoxia and HDAC inhibitors in cardiac myocytes

Huaping Shi, Lei Chen, Huilan Wang, Shoukang Zhu, Chunming Dong, Keith A. Webster, Jianqin Wei

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

HDAC inhibitors are under clinical development for the treatment of hypertrophic cardiomyopathy and heart failure although the mechanisms of protection are incompletely understood. Micro-RNA 126, an endothelium-specific miR has been assigned essential developmental roles in the heart by activating survival kinases ERK1/2 and Akt and increasing pro-angiogenic signaling. Here we provide the first evidence that hypoxia and HDAC inhibitors selectively and synergistically stimulate expression of miR-126 in cardiac myocytes. MiR-126 expression was increased 1.7-fold (p<. 0.05) after 1. h of hypoxic exposure and this was further enhanced to 3.0-fold (p<. 0.01) by simultaneously blocking HDAC with the pan-HDAC inhibitor Tricostatin A (TSA). TSA alone did not increase miR-126. In parallel, hypoxia and TSA synergistically increased p-ERK and p-Akt without effecting VEGF-A level. Knockdown of miR-126 with si-RNA eliminated inductions of p-ERK and p-Akt by hypoxia, whereas miR-126 overexpression mimicked hypoxia and amplified p-ERK and p-Akt in parallel with miR-126. The results suggest that miR-126 is a hypoxia-inducible target of HAT/HDAC and its activation in cardiac myocytes may contribute to cardioprotection by activating cell survival and pro-angiogenic pathways selectively during ischemia.

Original languageEnglish (US)
Pages (from-to)827-832
Number of pages6
JournalBiochemical and biophysical research communications
Volume430
Issue number2
DOIs
StatePublished - Jan 11 2013

Keywords

  • Cardiac myocytes
  • HDAC inhibitor
  • Hypoxia
  • Micro-RNA-126
  • Tricostatin A

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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